Brain damage occurs in over 60% of chronic alcoholics. The causes and pathophysiology of this damage, however, are poorly understood. The general goal of our research has been to evaluate the factors that lead to alcohol-induced degeneration of the nervous system in experimental animals. It is generally agreed that at least one type of alcohol-induced brain damage, Wernicke-Korsakoff's encephalopathy, is due to alcohol-induced thiamine deficiency. We have therefore studied the effect of thiamine deficiency on rat brain. Thiamine-deficient rats exhibited a breakdown of the blood brain barrier as evidenced by small hemorrhages and an accumulation of blood proteins in the brain. Biochemically these brains demonstrated an accumulation of proteins normally found in the blood; for example, albumin, fibrinogin, and hemoglobin. The breakdown of the blood brain barrier may lead to some of the irreversible brain damage and neurological deficits associated with thiamine deficiency. The role of calcium ions in the degeneration of nervous tissue is being investigated in the squid giant axon. In the squid axon we have identified a number of immunoreactive degradation products after calcium-activated proteolysis. The results suggest that an elevation of cytosolic ionized calcium may result in a breakdown of proteins.